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Gap junctions in cardiovascular disease

H J Jongsma1, R Wilders

  • 1Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands. h.j.jongsma@med.uu.nl

Circulation Research
|June 24, 2000
PubMed

Insights

Cardiac gap junction remodeling, a change in connexin distribution, has minimal impact on conduction velocity. Cellular geometry and cytoplasmic resistivity are more critical factors in cardiac electrical signal propagation.

Area of Science:

  • Cardiovascular Physiology
  • Biophysics
  • Cardiac Electrophysiology

Background:

  • Connexins form gap junction channels crucial for cardiac electrical coupling.
  • Cardiac diseases often involve "gap junction remodeling," altering connexin distribution.
  • This remodeling is hypothesized to be arrhythmogenic, potentially causing arrhythmias.

Purpose of the Study:

  • To investigate the impact of quantitative gap junction remodeling on cardiac conduction velocity and anisotropy.
  • To determine the relative importance of connexin remodeling versus cellular properties in cardiac electrophysiology.

Main Methods:

  • Utilized a simplified computational model of human ventricular myocardium.
  • Incorporated quantitative remodeling data for connexin number and distribution from existing literature.
  • Simulated electrical signal propagation to assess conduction velocity and anisotropy ratio.

Main Results:

  • Cardiac gap junction remodeling resulted in only small to moderate changes in conduction velocity and anisotropy.
  • Cytoplasmic resistivity and cellular geometry were found to be significantly more influential on longitudinal conduction than remodeling.
  • No simulated remodeling scenario produced conduction velocities as slow as a few cm/s.

Conclusions:

  • The arrhythmogenic potential of gap junction remodeling may be overestimated.
  • Cellular properties, particularly cytoplasmic resistivity and geometry, play a dominant role in determining cardiac conduction.
  • Further research should focus on these cellular factors in understanding cardiac electrophysiology and disease.

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